Phosphorylation

In biochemistry, phosphorylation is the reversible introduction of one or more phosphoryl groups into organic molecules or macromolecules (e.g. into proteins or nucleic acids) under the catalytic action of enzymes (mostly kinases; protein kinases). Chemically, this process involves the formation of a phosphoric acid ester.

Phosphorylations often occur by transferring phosphate residues of energy-rich phosphates (adenosine triphosphate, phosphoenolpyruvate, creatine phosphate, etc.) to the corresponding molecules. The result is called "phosphoprotein".

This form of phosphorylation represents (besides allosteric and competitive inhibition) the most important regulation of biological processes in the cell.

ATP is formed in the respiratory chain from ADP (adenosine-5'-diphosphate) by so-called respiratory chain phosphorylation (oxidative phosphorylation), in photosynthesis by photophosphorylation.

Phosphorylation of proteins: In this process, a phosphate group is enzymatically bound to an amino acid residue, with mainly ATP serving as substrate for the phosphate. The responsible enzymes are called kinases. Another group of enzymes, the phosphatases, can reverse this process, i.e. the phosphate group is enzymatically split off from the phosphorylated protein. Protein kinases and protein phosphatases are usually very specific. Their activity can be specifically controlled.

Function: Phosphate groups have a polar charge. The enzymatic transfer of a phosphate group to a molecule by kinases usually results in a conformational change of the protein, usually combined with a functional change. Thus, phosphorylation can lead to an activation of a protein. Many transcription factors are activated in this way via signal transduction cascades. Another form of influence by phosphorylation is the control of protein binding sites. In particular, protein domains that mediate these interactions are phosphorylated and are thus no longer able to form protein complexes. Many receptors, such as G-protein coupled receptors, are regulated in their activity in this way. Protein phosphorylation and dephosphorylation thus have a regulatory function.

Location of phosphorylation: In proteins, three amino acids are phosphorylated, namely those with a hydroxy group in the side chain. The kinase in question is named after its substrate, e.g. tyrosine kinase, serine kinase, etc.

• Tyrosine: Tyrosine kinases thus bind the phosphate group to tyrosine
• Serine/threonine: Serine/threonine kinases bind the phosphate group to serine or threonine. Serine is the most frequently phosphorylated amino acid (ratio of the phosphorylation frequency of serine: threonine: tyrosine = 1800: 200: 1).
• Very rarely the amino acids histidine, arginine, lysine, cysteine, glutamate and aspartate are phosphorylated.

Phosphorylation of other molecules: If other molecules (sugars, nucleotides) are phosphorylated, this usually serves to provide chemical energy in the molecule to enable energy-consuming conversions in subsequent steps.

Polyphosphates such as ATP or creatine phosphate serve in the metabolism as a universal "energy currency" for intermediate storage and exchange of energy between different processes.